Clinical Study On The Treatment Of α-synuclein Disease With White Matter Hyperintensity By Wenshen Jiannao Prescription Combined With DT

Alpha synucleinopathy（α-synucleinopathy）,a neurodegenerative disorder,is common in middle-aged or older people.And it is characterized by motor disorders such as progressive myotonia and non-motor disorders such as dementia and bowel and bladder dysfunction.White Matter Hyperintensity（WMH）is also a neurological disorder and often found in middle-aged or older people,with the main clinical manifestations of cognitive impairment,bowel and bladder dysfunction,and gait disorders.Several studies have confirmed that patients may have both of them.But this is seldomly reported worldwide and systematic treatment options are yet to be provided.Our research group found that both Parkinson’s disease（PD）and Multiple System Atrophy（MSA）that are associated with a-synucleinopathy are caused by Xuqiliuzhi and Shenxusuijian,and the core pathogenesis of WMH is Luosunsuishang.Based on this,this study suggests that α-synucleinopathy and WMH share the core pathogenesis of Xuqiliuzhi and Shenxusuijian.In addition,to find the link betweenα-synucleinopathy and WMH,this study investigated the clinical characteristics ofα-synucleinopathy in combination with WMH based on clinical scales and Diffusion Tensor Imaging（DTI）to provide a basis for a comprehensive assessment of clinical symptoms.Our previous study demonstrated that the method of tonifying the kidney and nourishing marrow can effectively reduce some of the clinical symptoms of α-synucleinopathy and WMH and slow down the disease progression.This study aims to investigate the efficacy of Chinese herbal medicine in the treatment of a-synucleinopathy combined with WMH through the method of Bushenyisui.Objectives:Study 1:This study aims to develop a better understanding of α-synucleinopathies and WMH from the aspect of Xuqiliuzhi and proposes that the core pathogenesis of both diseases is Xuqiliuzhi,to provide a theoretical basis for the treatment of the two diseases by Zishenyisui.Study 2:This study compares the clinical manifestations of a-synucleinopathy with WMH and without WMH and DTI imaging features to provide a basis for clinical evaluation of the diseases.Study 3:This study investigates the efficacy of Wenshenjiannaofang by comparing the symptoms before and after the treatment and using the Chinese and Western clinical scales and DTI,to provide a clinical basis for the treatment of the diseases.Methods:Study 1:This study aims to develop a better understanding a-synucleinopathy combined with WMH from the perspective of Xuqiliuzhi.This study discusses the etiology and pathogenesis of MSA,PD,and WMH and proposes that the core pathogenesis of both α-synucleinopathy and WMH is Xuqiliuzhi and Shenxusuijian,and they can be treated together.In addition,we proposed treatment principles and methods to based on Xuqiliuzhi.Study 2:Clinical characteristics of a-synucleinopathy in combination with WMHIn this study,patients with MSA and PD were included according to the inclusion criteria,and all patients were evaluated by demography and Chinese and Western medical scales.Some patients were selected to take DTI examination.Besides,fractional anisotropy（FA）values and mean diffusivity（MD）coefficients were selected as indicators to assess the clinical characteristics of a-synucleinopathy in combination with WMH.Study 3:This study investigates the treatment of α-synucleinopathy combined with WMH with Wenshenjiannaofang.Patients with α-synucleinopathy combined with WMH were included in this study,and they were treated orally with the Wenshenjiannaofang based on the symptomatic treatment with Western medicine like anti-Parkinsonian drugs,butyphthalide,coenzyme Q10.The treatment lasted 3 months.The patients were also evaluated on the Chinese and Western medical scales at the time of enrollment and 3 months after treatment.Some patients were examined by DTI before and after treatment.Results:Study 1:This study proposes that Shenxusuijian and Xuqiliuzhi are the pathological findings in MSA,PD,and WMH.With the concept of holism in TCM,α-synucleinopathy and cerebral white matter demyelination can be discussed together.Scholars also believe that tremor and dementia share common pathological findings that include Xuqiliuzhi and Shenxusuijian.So they can be discussed together.In terms of treatment with TCM,both Chenzheng and Chidai can be treated by Bushenyisui.And positive clinical treatment outcomes can be found in patients treated by Bushenyisui.Study 2:Forty-seven patients with PD and 159 patients with MSA were included in this study.Patients with a Fazekas score ≥1 had higher NMSS scores and lower MoCA scores compared with patients with a Fazekas score of 0（all P<0.05）.WMH severity in patients with PD was significantly associated with sleep/fatigue and attention/memory scores on the NMSS subscale（P<0.05）.Patients with a Fazekas score ≥1 had higher NMSS scores and lower MoCA scores compared with patients with a Fazekas score of 0（all P<0.05）.WMH severity was significantly correlated with sleep/fatigue,attention/memory,and voiding disorders on the NMSS subscale in MSA patients with WMH（P<0.05）.A total of 69 cases with α-synucleinopathy（PD+MSA）underwent DTI,33 of which had WMH and 36 did not have WMH.No significant differences were seen in FA values of all 72 fiber tracts（P>0.05）.Differences were found in the MD values of the left prefrontal-thalamic fiber tracts and the left prefrontal-striatal fiber tracts（P<0.05）.Study 3:A total of 58 MSA patients with WMH and 31 PD patients with WMH were included in this study.PD patients with WMH had lower scores on the NMSS scale and TCM scale for cerebrospinal diseases after treatment,with statistically significant differences（P<0.05）.Sleep/fatigue scores on the NMSS scale improved after treatment in PD patients with WMH（P<0.05）.MSA patients with WMH had lower scores on the NMSS scale and TCM scale,with statistically significant differences（P<0.05）.Scores of sleep/fatigue,emotion/cognition,and gastrointestinal symptoms on the NMSS scale improved after treatment in MSA patients with WMH（P<0.05）.A total of 16 cases with α-synucleinopathy（PD+MSA）took DTI examination before and after treatment.The FA values of four fiber tracts including CC₅,IFO_left,ILF_right,and OR_left were lower than those before the treatment（P<0.05）.And the MD values of three fiber tracts including CST_right,ICP_right,and MCP were higher than those before the treatment（P<0.05）.Conclusion:Study 1:Both α-synucleinopathy and WMH share a pathogenesis of Xuqiliuzhi and Bushenyisuitongluo is an effective treatment option.Study 2:Compared with α-synucleinopathy patients without WMH,those with WMH can experience more serious cognitive disorders and bowel and bladder dysfunction,which may be associated with the frontal-striatal-thalamic loop.Study 3:Wenshenjiannaofang can slow down the progression of α-synucleinopathy and effectively improve some of the non-motor symptoms of patients.This may be related to the protection of the prefrontal-striatal-thalamic loop structure by the treatment with TCM.